July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Metabolomics reveals changes in fatty acid metabolism in age-related macular degeneration patients
Author Affiliations & Notes
  • Milam A Brantley
    Ophthalmology & Visual Sciences, Vanderbilt University Medical Center, Brentwood, Tennessee, United States
  • Karan Uppal
    Medicine, Emory University Medical Center, Atlanta, Georgia, United States
  • Chunyu Ma
    Medicine, Emory University Medical Center, Atlanta, Georgia, United States
  • Anita Agarwal
    Ophthalmology & Visual Sciences, Vanderbilt University Medical Center, Brentwood, Tennessee, United States
  • Margaret A Pericak-Vance
    John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, United States
  • William K Scott
    John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, United States
  • Jonathan L Haines
    Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, United States
  • Dean Jones
    Medicine, Emory University Medical Center, Atlanta, Georgia, United States
  • Sabrina L Mitchell
    Ophthalmology & Visual Sciences, Vanderbilt University Medical Center, Brentwood, Tennessee, United States
  • Footnotes
    Commercial Relationships   Milam Brantley, None; Karan Uppal, None; Chunyu Ma, None; Anita Agarwal, None; Margaret Pericak-Vance, None; William Scott, None; Jonathan Haines, None; Dean Jones, None; Sabrina Mitchell, None
  • Footnotes
    Support  NIH Grants R01 EY22618 and R01 EY012118
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 1187. doi:
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    • Get Citation

      Milam A Brantley, Karan Uppal, Chunyu Ma, Anita Agarwal, Margaret A Pericak-Vance, William K Scott, Jonathan L Haines, Dean Jones, Sabrina L Mitchell; Metabolomics reveals changes in fatty acid metabolism in age-related macular degeneration patients. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1187.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To identify metabolic pathways altered in patients with age-related macular degeneration (AMD) and determine pathways specifically affected in intermediate AMD (IAMD) and neovascular AMD (NVAMD).

Methods : We performed untargeted metabolomics using high-resolution LC-MS on plasma from 191 AMD patients (IAMD=91, NVAMD=100) and 195 controls. The mass spectrometer was set to capture mass to charge ratio from 85 to 1985 over 10 minutes. Metabolic features were extracted using apLCMS and xMSanalyzer. Partial least squares discriminant analysis (PLS-DA) was used to identify features that discriminate between groups in each comparison. Those features with a variable importance for projection (VIP) ≥ 2 were further assessed using linear models for microarray data (limma) to prioritize features for verification by tandem mass spectrometry. Additionally, pathway analysis was performed with Mummichog on those features identified by PLS-DA with VIP ≥ 1.5.

Results : After data preprocessing and filtering, more than 6,300 features were available for downstream analyses in each of the three comparisons. When comparing AMD patients to controls, 351 discriminating features were identified. The carnitine shuttle (p<1.0 x 10-5) and prostaglandin formation from dihomo-gamma-linoleic acid (p=1.1 x 10-4) pathways were altered in AMD patients compared to controls. When comparing IAMD patients to controls, 284 discriminating features were identified. Seven pathways were altered in IAMD patients compared to controls. The two most significant were the carnitine shuttle (p=0.015) and saturated fatty acid beta-oxidation (p=0.026) pathways. Additional pathways included amino acid metabolism and glycosphingolipid metabolism. When comparing NVAMD patients to IAMD patients, 280 discriminating features were identified. Pathway analysis revealed alterations of the carnitine shuttle pathway (p<1.0 x 10-5) and the saturated fatty acid beta-oxidation pathway (p=0.048) in NVAMD patients compared to IAMD patients

Conclusions : These results demonstrate that fatty acid metabolism is altered in AMD patients, and these alterations are greater in NVAMD patients. This suggests that changes in fatty acid metabolism may contribute to the pathogenesis of NVAMD and represent a potential target for clinical monitoring or intervention.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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